Regulation of the cytokine profile of NK cells by microenvironment factors typical for pregnancy

Abstract

Decidual NK cells, found in area of uteroplacental contact, exhibit distinct phenotypic and functional characteristics compared to NK cells present in peripheral blood. However, mechanisms underlying development of these unique properties remain poorly understood. It is postulated that microenvironmental cells exert both direct and indirect influence on NK cells within the uterus, modulating their level of "aggressiveness" towards fetal tissues, including trophoblasts.One of mechanisms of remote regulation of NK cells is release of cytokines. Trophoblasts, as well as other elements of the microenvironment, such as uterine macrophages or endometrial cells, produce biologically active molecules called cytokines. These cytokines bind to receptors on the surface of target cells, triggering a series of signaling cascades that lead to changes in the behavior of NK cells. As a result, NK cells themselves can release cytokines, which in turn influence the behavior of other cells in the vicinity. As mentioned previously, there is a lack of data on causes and mechanisms behind changes in characteristics of NK cells in uterus. Nevertheless, this data can form the foundation for creating a more accurate cellular model of interaction between fetal cells and the mother's immune system. Additionally, it can serve as a basis for developing diagnostic tools for reproductive issues.The aim of the study was to investigate changes in the cytokine profile of NK cells, specifically their production of TNFα, TGFβ, IFNγ, RANTES, IL-10, and VEGF under the influence of cytokines associated with pregnancy – TNFα, IFNγ, TGFβ1, IL-15, IL-18, or IL-10.The levels of these cytokines in the conditioned media of NK cells were measured using flow cytometry. It was found that transforming growth factor β1 (TGF-β1), produced by trophoblasts, has the ability to regulate NK cell secretion. Under its influence, the levels of IFNγ, IL-10, and RANTES in the media derived from NK cell culture decreased.Based on these findings, it can be inferred that there exists a system involving decidual NK cells and trophoblast cells that controls excessive or insufficient activity of NK cells via the cytokine network. These data suggest the potential for using TGFβ1 to model interaction between NK cells and trophoblasts in vitro.